A number of issues confound treatment of carcinomas. First, most deaths from carcinomas (˜90%) result from metastatic spread of the disease to distant sites rather than from the primary tumors; in the case of breast cancer, nearly all deaths result from metastatic dissemination. Second, the development of therapeutic resistance to initially treated tumors results in the relapse of cancers into more aggressive forms that are even more difficult to contain. Both of these properties of aggressive carcinomas can be traced to intrinsic intratumoral heterogeneity, which can arise through various mechanisms, prominent among these being the presence of subpopulations of more mesenchymal CSCs in carcinomas.
As one example, breast cancer is one of the most common cancers in women, accounting for over 30% of all cancer incidence in women in the United States. Basal-like breast cancers account for 8-20% of incident breast cancers and stain negatively for ER (estrogen receptor) and HER2 and stain positively for cytokeratin. Despite various definitions of this subtype of breast cancer and its heterogeneous nature, a unifying property is the poor clinical outcome of patients suffering from this disease, which results from its aggressive clinical history and strong association with the development of metastatic relapse. The standard-of-care for basal-like breast cancers has remained largely unchanged, continuing to rely on conventional radio- and chemotherapy, partly be due to the lack of highly specific markers to adequately characterize the genetic and epigenetic heterogeneity of this subtype, which is currently based essentially on exclusion of markers such as ER, PR (progesterone receptor) and HER2.